澳大利亚墨尔本大学Melissa H. Little、Sara E. Howden等研究人员合作发现，来自人肾脏类器官的远端肾单位上皮具有双重可塑性。这一研究成果于2020年12月29日在线发表在国际学术期刊《细胞—干细胞》上。

通过重新分析人类胎儿肾脏中远端肾单位和输尿管上皮之间的转录差异，研究人员发现，尽管现有的含有肾单位的肾脏类器官包含远端肾单位上皮且没有输尿管上皮，但仅此远端肾脏部分显示出显著的体外可塑性，并且在限定条件下分离和培养时，可形成输尿管上皮尖端的细胞身份。“诱导型”输尿管上皮培养物能够冷冻保存，且连续传代而不会失去一致性，并向收集导管的命运过渡。此外，在PKHD1中具有功能丧失突变的培养物也涵盖了与常染色体隐性多囊性肾脏疾病相关的囊性表型。

据悉，在发育过程中，与肾脏的输尿管上皮相比，不同的祖细胞参与了肾单位的形成。实际上，以往人类多能干细胞来源的肾脏组织模型要么包含肾单位，要么包含特定于输尿管上皮的模式。

附：英文原文

Title: Plasticity of distal nephron epithelia from human kidney organoids enables the induction of ureteric tip and stalk

Author: Sara E. Howden, Sean B. Wilson, Ella Groenewegen, Lakshi Starks, Thomas A. Forbes, Ker Sin Tan, Jessica M. Vanslambrouck, Emily M. Holloway, Yi-Hsien Chen, Sanjay Jain, Jason R. Spence, Melissa H. Little

Issue&Volume: 2020-12-29

Abstract: During development, distinct progenitors contribute to the nephrons versus the uretericepithelium of the kidney. Indeed, previous human pluripotent stem-cell-derived modelsof kidney tissue either contain nephrons or pattern specifically to the ureteric epithelium.By re-analyzing the transcriptional distinction between distal nephron and uretericepithelium in human fetal kidney, we show here that, while existing nephron-containingkidney organoids contain distal nephron epithelium and no ureteric epithelium, thisdistal nephron segment alone displays significant in vitro plasticity and can adopt a ureteric epithelial tip identity when isolated and culturedin defined conditions. “Induced” ureteric epithelium cultures can be cryopreserved,serially passaged without loss of identity, and transitioned toward a collecting ductfate. Cultures harboring loss-of-function mutations in PKHD1 also recapitulate the cystic phenotype associated with autosomal recessive polycystickidney disease.

DOI: 10.1016/j.stem.2020.12.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30585-3